SUMMARY: Breast cancer is the most common cancer among women in the US and about 1 in 8 women (12%) will develop invasive breast cancer during their lifetime. Approximately, 246,660 new cases of invasive breast cancer will be diagnosed in 2016 and 40,450 women will die of the disease. Patients with early stage breast cancer often receive adjuvant chemotherapy. Chemotherapy recommendations for early stage breast cancer are often made based on tumor size, grade, hormone receptor and HER-2 status, immunohistochemical markers such as Ki-67, nodal status, patients age, menopausal and performance status. Adjuvant! Online is one of the tools that incorporates these features and assists in treatment decision making. This tool however does not take into account individual tumor molecular signatures which can better predict clinical outcomes. MammaPrint® is a 70-gene signature assay approved by the FDA and is able to distinguish low risk and high risk tumors based on the risk of distant recurrence at 5 and 10 years. The authors in this study selected patients for adjuvant chemotherapy utilizing 70-gene signature assay in addition to standard clinicopathological criteria and prospectively reported 5-year outcomes in the treatment groups.
MINDACT (Microarray in Node-Negative and 1 to 3 Positive Lymph Node Disease May Avoid Chemotherapy) study is a international, prospective, randomized, phase III study which enrolled 6693 women with early-stage breast cancer and determined their genomic risk using the 70-gene signature assay (MammaPrint®) and their clinical risk using a modified version of Adjuvant! Online. Enrolled patients were divided into four groups based on their clinical and genomic risk: low clinical risk and low genomic risk (N=2745, 41%); high clinical risk and high genomic risk (N=1806, 27%), high clinical risk and low genomic risk (N=1550, 23.2%); low clinical risk and high genomic risk (N=592, 8.8%). Patients in the first 2 concordant groups were treated according to their risk category, ie. low-risk group did not receive adjuvant chemotherapy whereas adjuvant chemotherapy was added to endocrine therapy following surgery, in the high-risk patient group. Patients in the last 2 discordant groups were randomly assigned to receive adjuvant chemotherapy or no chemotherapy. The median age of the patients was 55 yrs, 79% of the patients had node-negative disease and 21% had 1-3 positive nodes. A total of 88% of the tumors expressed ER, PR, or both, and 9.5% were HER-2 positive.
The primary endpoint of this study was to show noninferiority against a predefined benchmark of a 5-year metastasis-free survival rate of 92%, in patients at high clinical risk, for whom a discordant low genomic risk led to the omission of otherwise standard adjuvant chemotherapy. It was noted that in this group of patients at high clinical risk and low genomic risk (N=1550) at 5 years, the rate of survival without distant metastasis was 94.7% among those not receiving chemotherapy, and this met the study criterion for noninferiority, with similar outcomes noted in all sub groups of patients.. The absolute difference in the survival rate between those who did not receive adjuvant chemotherapy and those who received chemotherapy was 1.5%, with the survival rate slightly higher in those who received adjuvant chemotherapy. The 5-year metastasis-free survival rate for women who were low risk by both genomic and clinical criteria and who did not receive adjuvant chemotherapy was 97.6%, compared with 90.6% for those women who were high risk by both criteria and who did receive adjuvant chemotherapy.
It was concluded that in patients with early stage breast cancer, who were considered to be at high clinical risk for recurrence, 70-gene signature assay was able to identify those with low genomic risk, who had marginal benefit with adjuvant chemotherapy. With treatment guidance using 70-gene signature assay, approximately 46% of early stage breast cancer patients with high clinical risk and low genomic risk might not require adjuvant chemotherapy. 70-Gene Signature as an Aid to Treatment Decisions in Early-Stage Breast Cancer. Cardoso F, van’t Veer LJ, Bogaerts J, et al. N Engl J Med 2016; 375:717-729
